Lurbinectedin shows promise as second-line therapy for SCLC

Medical writer: Tim Donald, ELS

Lurbinectedin, an inhibitor of activated transcription, showed notable anti-tumour activity as a second-line treatment in small cell lung cancer (SCLC) in a phase II clinical trial, according to a June 1 presentation (Abstract 8506).

“Lurbinectedin is an active single agent in second-line SCLC,” said presenter Luis G. Paz-Ares, MD, PhD, of Hospital Universitario 12 de Octubre, CNIO, and Universidad Complutense and Ciberonc, Spain. “Anti-tumour activity has been observed in sensitive patients, with an overall response rate [ORR] of 45%. But also, in a setting where we have very few opportunities for treatment, in the setting of resistance, with ORR of 22.2%.”

In addition, the safety profile was favorable, and side effects were easily managed, he said. There were low percentages of treatment-related serious adverse events (SAEs) and of discontinuation due to adverse events (AEs), and there were no toxic deaths.

“With these data, we may conclude that lurbinectedin is emerging as a potential new [second-line] treatment alternative for SCLC,” he said.

Lurbinectedin’s anti-tumour activity in SCLC was first observed in a phase I/II study in combination with doxorubicin. The study Dr. Paz-Ares presented is a phase II basket trial assessing the efficacy of lurbinectedin in several cancer types, including SCLC. The primary endpoint was ORR by RECIST V.1.1. For the SCLC cohort, a target ORR of 30% or greater was set.

Patients included had at least one prior chemotherapy line and adequate organ function. Patients with prior immunotherapy could be included. Patients with central nervous system metastasis were excluded. Patients received lurbinectedin 3.2 mg/m² as a 1-hour intravenous infusion on day 1 every 3 weeks.

In addition to assessing the total population, investigators stratified patients into resistant (chemotherapy-free interval [CTFI] < 90 days) and sensitive (CTFI ≥ 90 days) groups. In the total population (105 patients), ORR was 35.2% (95% CI [26.2, 45.2]). Median duration of response (mDoR) was 5.3 months (95% CI [4.1, 6.4]).

In resistant patients, ORR was 22.2% (95% CI [11.2, 37.1]), and mDoR was 4.7 months (95% CI [2.6, 5.6]). In sensitive patients, ORR was 45.0% (95% CI [32.1, 58.4]), and mDoR was 6.2 months (95% CI [3.5, 7.3]).

Median progression-free survival (PFS) in the total population was 3.9 months (95% CI [2.6, 4.6]). In the resistant population, PFS was 2.6 months (95% CI [1.3, 3.9]), and in the sensitive population, it was 4.6 months (95% CI [3.0, 6.5]).

Median overall survival (OS) in the total population was 9.3 months (95% CI [6.3, 11.8]). In the resistant population, OS was 5.0 months (95% CI [4.1, 6.3]), and in the sensitive population it was 11.9 months (95% CI [9.7, 16.2]).

Regarding safety, in the 105 patients, there were 11 SAEs (10.5%), with two (1.9%) leading to discontinuation. Most AEs were less than grade 3. Most grade 3/4 treatment-related AEs were hematologic. The most frequent nonhematologic AEs were grade 1/2 fatigue and nausea.

Discussant Anna F. Farago, MD, PhD, of Massachusetts General Hospital, thanked the study authors for “focusing on a disease where we still have tremendous unmet clinical need.” She noted that, although cross-study comparisons have limited value, the ORR and median OS data in the lurbinectedin study compare well to recent randomized studies assessing topotecan and amrubicin.

Especially regarding the ORR of 35.2%, she said, “Here, lurbinectedin does stand out as being numerically higher than the responses we’ve seen in these other studies.”

Regarding limitations of the study, Dr. Farago said it is a single-arm phase II study, and the OS data are immature, as one-third of the patients are still in follow-up. In addition, she said there are questions about how the “shifting standards for first-line therapy”—with more patients receiving combined chemotherapy and immunotherapy—are affecting patient responses to second-line therapies.

Lurbinectedin has received orphan drug designation from the U.S. Food and Drug Administration, she noted, but phase III study data are needed. A 600-patient phase III study comparing doxorubicin plus lurbinectedin to either topotecan or cyclophosphamide/doxorubicin/vincristine, with a primary endpoint of OS, has completed enrolment.



Posted on 15 July, 201925 March, 2021